PALB2 mutations shown to be important risk factor for breast cancer

1. Women with PALB2 mutations were 4 to 9 times more likely to be diagnosed with breast cancer when compared to the general population. 

2. About a third of women with PALB2 mutations developed breast cancer by the age of 70.

Evidence Rating Level: 2 (Good)

Study Rundown: PALB2 encodes a protein that is essential to BRCA2 function and that has been shown to interact with BRCA1. Loss-of-function mutations in PALB2 have been associated with increased risk of breast cancer. This study, involving multiple centers around the world, is one of the largest effort to date to estimate the cancer risk associated with PALB2 loss-of-function mutations.

This study examined over 300 women from families with this mutation to determine how much the PALB2 mutation contributes to breast cancer risk. The results show that PALB2 mutations place women at high risk of breast cancer. Depending on age, women with these mutations had an approximately 4 to 9 times increased risk of breast cancer compared to the general population. By age 70, these women had a 35% risk of developing breast cancer; this risk was as high 58% in women who have family members with breast cancer. For comparison, the risk of breast cancer by age 70 in women with BRCA1 and BRCA2 mutations is about 49 to 57%.

Click to read the study, published today in NEJM

Click to read the accompanying editorial in NEJM

Relevant Reading: Meta-Analysis of BRCA1 and BRCA2 Penetrance

In-Depth [retrospective cohort]: The study includes 362 subjects: 311 women and 51 men with confirmed PALB2 mutations. Among these subjects, 229 of the women and 7 of the men had breast cancer. Based on their data, the authors were able to estimate age-specific risk for PALB2 mutation carriers. The annual incidence of breast cancer ranged from 0.01% per year among 20-24 year-olds to 1.34% per year among 70-74 year-olds. The relative risk of breast cancer was highest in the youngest age group, 9.01 (95% confidence interval), and lowest in the oldest age group 4.56 (95% confidence interval). A family history of breast cancer also increased risk, especially having a mother and a sister who developed breast cancer by age 50.

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